Isotechnika Inc. said Thursday it began a Phase III trial of its lead candidate, ISA247, for psoriasis.
A day earlier, the Edmonton, Alberta-based company received Canadian regulatory approval to start the study, which is scheduled to last 24 weeks and include 400 people with a severe form of the condition. To date, 21 patients have been recruited.
"It's a major milestone for this company," Randall Yatscoff, Isotechnika's president and chief operating officer, told BioWorld Today. "The finish line is much closer. Not many drugs get to Phase III and get approval to move forward, so we're very excited about that. The company will be viewed in a different perspective."
The multicenter, double-blind trial will randomize 100 subjects to a high-dose group (0.4 mg/kg twice daily) of ISA247. Another 100 will receive the anticipated therapeutic dose (0.3 mg/kg twice daily), 100 more will receive a low dose (0.2 mg/kg twice daily) and the final 100 will get placebo. Those on placebo for the first 12 weeks will receive the 0.3-mg/kg twice-daily dose beginning in week 13. All doses are to be administered orally as soft gelatine capsules.
The study's primary endpoint is a measure of the proportion of subjects who achieve a 75 percent reduction in their Psoriasis Area and Severity Index (PASI) score. Secondary endpoints include maintenance of stable kidney function and assessment of quality of life. Blood specimens will be collected periodically to gather additional pharmacokinetic and pharmacodynamic data.
"We should have interim Phase III data in the latter part of next summer," Yatscoff said. "The next step will be filing with the FDA for a Phase III [trial] early next year, and we'll have one going in the U.S. in the latter part of next year."
Two pivotal studies are required for registration in the U.S. and Canada, and he added that a U.S. trial might only have two or three arms but be placebo-controlled. To line up the product for European approval, Isotechnika expects to conduct a third pivotal trial to compare ISA247 to cyclosporine, a product not frequently used for psoriasis in the U.S. or Canada.
Results of a Phase II psoriasis trial of the immunosuppressant showed that 74 percent of the 200 patients in the study exhibited a 75 percent reduction in their PASI score. Yatscoff said that data give the company confidence moving into later-stage studies.
"[We will license the product] if the right deal comes along," he added. "We've been approached by a number of companies, but we don't have to rush anything, as our cash position is such that we don't need something immediately. But for psoriasis, the goal is to enter into licensing deals down the line."
Among suitors for the product's rights are some of the companies that sell injectable biologics for psoriasis, he said. Products that in recent years have reached the market include Enbrel (etanercept, Amgen Inc. and Wyeth), Amevive (alefacept, Biogen Idec Inc.), Remicade (infliximab, Centocor Inc.) and Humira (adalimumab, Abbott Laboratories).
Yatscoff noted that in addition to the difference in delivery between ISA247 and the biologics, the biologics are not as potent, cost more and cause more side effects. As a result, Yatscoff said ISA247 stands a good chance of taking a share of the psoriasis market from the biologics.
Isotechnika owns the product's rights for all autoimmune diseases, and expects to evaluate its use in lupus and other disorders down the road.
ISA247 also has been tested in a Phase IIa study for kidney transplantation. That program is partnered with F. Hoffmann-La Roche Ltd., of Basel, Switzerland. Isotechnika is responsible for conducting a Phase IIb study, scheduled to start late next year, with Roche more fully taking over responsibilities thereafter.
Outside of ISA247's development, Isotechnika recently expanded its pipeline to include two additional immunosuppressive compounds, TAFA93 and TKB662. The former is a small-molecule inhibitor of mTOR, a class of drugs used to prevent organ rejection in transplantation and as a coated stent therapy for coronary artery disease. Preclinical studies of the latter product have demonstrated its inhibition of T-cell and B-cell activation and proliferation through multiple mechanisms of action, including the inhibition of lymphocyte phosphorylation activity.
The company noted that both TAFA93 and TKB662 have distinct mechanisms of action from calcineurin inhibitors such as ISA247, meaning potential administration as complementary therapies in both prevention of organ rejection and treatment of autoimmune diseases.
In addition to its drug development programs, Isotechnika also operates a diagnostic division.